and Expression in Mouse Striatal Cholinergic Interneurons: Implications for Autism Spectrum Disorder

mice have been widely used to study the postnatal function of several genes in forebrain projection neurons, including cortical projection neurons (CPNs) and striatal medium-sized spiny neurons (MSNs). We linked heterozygous deletion of gene to autism spectrum disorder (ASD) and used mice to investigate the postnatal function of , which is expressed by CPNs but not MSNs. Recently, single-cell transcriptomics of the adult mouse striatum revealed the expression of in interneurons and showed expression in striatal cholinergic interneurons (SCINs), which are attracting increasing interest in the field of ASD. These data and the phenotypic similarity between the mice with haploinsufficiency and -dependent conditional deletion of () prompted us to better characterize the expression of and the activity of transgene in the striatum. Here, we show that the great majority of -expressing cells are SCINs and that all SCINs express . Using lineage tracing, we demonstrate that the transgene is expressed in the SCIN lineage where it can efficiently elicit the deletion of the floxed allele. Moreover, transcriptomic and bioinformatic analysis in mice showed dysregulated striatal expression of a number of genes, including genes whose human orthologues are associated with ASD and synaptic signaling. These findings identifying the expression of the transgene in SCINs lineage lead to a reappraisal of the interpretation of experiments using -dependent gene manipulations. They are also useful to decipher the cellular and molecular substrates of the ASD-related behavioral abnormalities observed in mouse models.